Protein kinase C (PKC) is a family of fourteen known isozymes found in varying ratios in the cytosolic and membrane fractions of cells, depending on the type of tissue and its physiological state (Nishizuka 1992 Science 258, 607.). PKC isozymes can be classified into three groups. Group I includes Ca2+ dependent isozymes: cPKC-alpha, cPKC-betaI cPKC-betaII and cPKC-gamma. Isozymes in group II, nPKC-epsilon, nPKC-delta, nPKC-eta and nPKC-theta are Ca2+ independent. Group III includes the atypical PKC: aPKC-iota (Selbie et al. 1993 J. Biol. Chem. 268, 24296), aPKC-zeta, aPKC-zetaII (Hirai et al. 2003 Neuroscience Lett. 348, 151), aPKC-mu (protein kinase D) and aPKC-nu (Hayashi et al. 1999 Biochim. et Biophys. Acta. 1450, 99) which are insensitive to both diacylglycerol and calcium and neither bind to nor are activated by phorbol esters. PKC regulates cellular functions, metabolism and proliferation by phosphorylating proteins in response to transmembrane signals from hormones, growth factors, neuro-transmitters and pharmacological agents.
Of special interest is atypical PKC-iota which does not contain a Ca2+-binding region, has one zinc finger-like motif and is the human homolog of the mouse PKC-lambda (Diaz-Meco et al. 1996 Molec and Cell Bio 16, 105). PKC-iota may play a role cellular malignancy as shown by its association with the transformed phenotype of human melanomas in vivo and in vitro (Selzer et al. 2002 Melanoma Research 12, 201) and by demonstrating that PKC-iota protects cells against drug induced apoptosis (Murray & Fields 1997 J. Biol. Chem. 272, 27521, Xie et al. 2000 Mol. Brain. Res. 82,107). In human lung cancer cells, PKC-iota is a Bad kinase that can phosphorylate and inactivate the proapoptotic BH3 protein leading to enhanced survival and chemoresistance (Jin et al. 2005).
The current method of detecting brain tumorigenesis is through biopsy and evaluation of tissue histology. It would be highly desirable to have a biomarker for the detection of brain tumorigenesis. Furthermore, it would be highly desirable to have a screening methodology to evaluate the proliferation rate of the detected tumor. Additionally, it would be highly desirable to have additional treatment regimens targeting the biochemical processes associated with tumorigenesis. The present invention provides systems and associated methodologies addressing these important needs.